Women With BRCA Mutations at Greater Risk for Recurrence, New Breast Tumors

For many women under 40 years of age with
breast cancer, surgery to remove the cancerous lump and accompanying
radiation therapy seem to be the best option for eradicating the
disease and preserving the natural breast. However, for women who
carry a damaged version of the BRCA1 or BRCA2 gene, thus predisposing
them to breast cancer, such treatment may be insufficient.
Researchers at Jefferson Medical College have found that these women
are at greater risk years later of either relapsing or developing new
tumors than are similarly treated women who do not carry one of these genes.

As a result, women and physicians may want to rethink their treatment
options said Bruce Turner, MD, PhD, who led the study and is
assistant professor of radiation oncology at Thomas Jefferson
University in Philadelphia and a member of Jeffersons Kimmel
Cancer Center.

Breast Conservation May Not Be Optimal Therapy for Mutation Carriers

These findings suggest that a woman who has a mutation in
BRCA1 or BRCA2 and who is treated with breast-conserving therapy not
only has a high risk of local recurrence40% according to our
studybut also a high risk of developing breast cancer in the
other breast as well, said Dr. Turner.

Our data suggest that breast-conserving therapy may not be
optimal treatment for breast cancer patients with BRCA1 or BRCA2
mutations who want to reduce the risk of locally recurrent breast
cancer. Dr. Turner and colleagues at Yale University and Myriad
Genetics reported their findings in the October 1999 issue of the Journal
of Clinical Oncology.

Of the 170,000 new breast cancer cases diagnosed annually in US
women, about 10%17,000 casesoccur in those under 40 years
of age. Some 10% to 15% of these women (2,000) carry an altered BRCA1
or BRCA2 gene, and about 70% to 80% develop breast cancer.

Dr. Turner and his group wanted to determine whether women with a
BRCA1 or BRCA2 mutation who are under 40 years of age and are likely
to develop breast cancer are more appropriately treated with
mastectomy or breast-conserving therapy.

The research team looked at the frequency of alterations in BRCA1 and
BRCA2 in 52 breast cancer patients who were treated with
breast-conserving lumpectomy and radiation between 1973 and 1994 and
who subsequently developed a recurrent cancer in the same breast.
They compared these women to 52 other women with localized breast
cancer who were treated similarly but did not develop recurrent disease.

The researchers found that 8, or 15%, of the 52 women who had further
breast cancer also carried a damaged BRCA1 or BRCA2 gene. In women 40
years of age or under with recurrent breast cancer, 6 of 15, or 40%,
had a mutated BRCA1 or BRCA2 gene. In contrast, only 1 of 15 women in
the comparison group who did not develop any recurrent cancers
carried the damaged gene.

The scientists also found that it took longeran average of
about 8 yearsfor women with an altered BRCA1 or BRCA2 gene to
relapse than it did for women without the damaged gene (slightly less
than 5 years on average). They then carefully examined the tumors
using molecular and histologic analysis, under the supposition that
these were old cancers that had returned. Instead, they found that
some of the tumors actually were completely new breast cancers. The
new cancers took an average of 8.5 years to develop.

BRCA Testing May Be Reasonable to Determine Optimal Treatment

If this study is validated with a larger prospective study, it
may suggest that BRCA1 or BRCA2 testing may be reasonable to
determine optimal breast cancer treatmenteither
breast-conserving therapy or mastectomyfor younger women with
family histories of breast or ovarian cancer, said Dr. Turner.

He believes that the study results may present women and their
physicians with some difficult decisions regarding appropriate
treatments. If you told a woman with a damaged BRCA1 or BRCA2
gene that in 9 years, 40% to 50% of patients like her are going to
have a new breast cancer, and she may need a mastectomy, then
youd have to ask her, would you rather have the lumpectomy and
7 weeks of radiation or would you rather have the mastectomy now and
reduce the risk of recurrent disease?

One problem with recurring cancer is the threat that the disease may
spread. While breast-conserving therapy may be curative for many
women, some women who develop recurrent breast cancer also develop
metastatic disease.

Dr. Turner said that researchers now need to look at the frequency of
chest wall relapse and metastatic disease in patients with BRCA1 or
BRCA2 who have had a mastectomy. It makes sense that by
removing 90% to 95% of the breast cancer cells by mastectomy, the
future risk of breast cancer is significantly reduced. But more
definitive data is needed before we can justify this recommendation.